The study will be conducted at 15-20 US centers in a randomized, placebo-controlled, double-blind fashion. Enrollees will be hospitalized sickle cell disease (SCD) patients at-risk for acute chest syndrome (ACS) based on the presence of vaso-occlusive crisis (VOC), fever (T ≥38.0°C) and serum sPLA2 concentration ≥50 ng/mL.

This is a double-blind randomized, parallel group, placebo-controlled dose escalation study (2 cohorts) in patients with sickle cell disease (SCD) and vaso-occlusive crisis (VOC) who are at-risk for development of acute chest syndrome (ACS) based on the combination of VOC, fever (T ≥38.0ºC), and a serum sPLA2 concentration ≥50 ng/mL.

The first group of patients will be randomized 2:1 to receive low dose A-001 or placebo as a 48-hour continuous infusion. Pharmacokinetic and clinical data from this group will undergo review by the Independent Data Monitoring Committee (IDMC). If there is no significant toxicity associated with A-001, then an additional group of patients will be enrolled and randomized 2:1 to high dose A-001 versus placebo as a 48-hour continuous infusion.

Patients are eligible for inclusion if they meet the following criteria:

• Sickle cell variant (Hb SS, Hb SC, sickle β°-thalassemia, sickle β+-thalassemia)
• Pain consistent with vaso-occlusive crisis
• Elevated serum sPLA2 level (measured on-site)
• Fever
• Age ≥5 years (through adult)

Patients must NOT meet any of the following exclusion criteria:

• New lung infiltrate by chest radiography
• Pregnancy or breastfeeding
• Significant renal dysfunction
• Significant hepatic dysfunction
• Acute neurologic dysfunction
• Any medical condition for which transfusion may be needed imminently, and/or hemoglobin <5 g/dL
• Red blood cell transfusion within 30 days of entry into the study